Natural Helper (NH) cells are newly discovered innate immune cells that produce T-helper type 2 (Th2) cytokines and promote protective type 2 immunity during helminth infection, or after influenza infection. The ontogeny of NH cells and their function in allergic diseases are not known. Strikingly, we find that NH cells have similar gene expression profile as T cell lineage progenitors, and that the development of NH cells is dependent on TCF-1, an essential transcription factor in early T cell development. We propose to determine the molecular pathways that underlie the development of NH cells. We will also examine the role of NH cells in the pathogenesis of allergic asthma. Studies in this proposal will improve our understanding of the generation and function of NH cells, which will inform therapeutic strategies to target NH cells for Th2 associated diseases.